IMPAM 23988
INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Unidad Ejecutora - UE
artículos
Título:
In Vitro , In Vivo , and In Silico Studies of Cumanin Diacetate as a Potential Drug against Trypanosoma cruzi Infection
Autor/es:
CERNY, NATACHA; MORALES, CELINA; DONADEL, OSVALDO J.; BEER, MARÍA F.; FABIAN, LUCAS; MALCHIODI, EMILIO L.; SÁNCHEZ ALBERTI, ANDRÉS; BIVONA, AUGUSTO E.; MOGLIONI, ALBERTINA; SÜLSEN, VALERIA P.
Revista:
ACS Omega
Editorial:
American Chemical Society
Referencias:
Lugar: Washington, DC ; Año: 2021
ISSN:
2470-1343
Resumen:
ABSTRACT: The sesquiterpene lactones cumanin, helenalin, andhymenin and their semisynthetic derivatives were evaluated againstTrypanosoma cruzi epimastigotes. The cytotoxicity of the compoundswas evaluated on murine splenocytes. Cumanin diacetate was one ofthe most active and selective compounds [IC50 = 3.20 ± 0.52 μg/mL,selectivity index (SI) = 26.0]. This sesquiterpene lactone was selectedfor its evaluation on trypomastigote and amastigote forms of theparasite. The diacetylated derivative of cumanin showed moderateactivity on trypomastigotes (IC50 = 32.4 ± 5.8 μg/mL). However, thiscompound was able to efficiently inhibit parasite replication with anIC50 value of 2.2 ± 0.05 μg/mL against the amastigote forms.Cumanin diacetate showed selectivity against the intracellular forms ofTrypanosoma cruzi with an SI value of 52.7. This cumanin analoguewas also active on an in vivo model of Chagas disease, leading to a reduction in the parasitemia levels in comparison with nontreatedanimals. Histopathological analysis of skeletal muscular tissues from treated mice showed only focal interstitial lymphocyteinflammatory infiltrates with slight myocyte necrosis; in contrast, nontreated animals showed severe lymphocyte inflammatoryinfiltrates with necrosis of the myocytes. A molecular docking study of cumanin and its derivatives on trypanothione reductase fromT. cruzi (TcTR) was performed. The results of ΔG docking achieved let the identification of diacetylated and O-alkylated derivativesof cumanin as good inhibitors of TcTR. Cumanin diacetate could be considered a potential candidate for further studies for thedevelopment of new therapies against Chagas disease.
